OBJECTIVE: The prevalence of cystic fibrosis–related diabetes (CFRD) has increased with improved life expectancy of patients. Clinical and care characteristics were compared with type 1 diabetes mellitus (T1DM) in a multicenter analysis of pediatric data. RESEARCH DESIGN AND METHODS: Auxological and treatment data from 47,227 patients aged younger than 21 years with CFRD or T1DM in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by multivariable mixed regression modeling. RESULTS: Diabetes onset (mean [interquartile range]) occurred later in individuals with CFRD (14.5 [11.8–16.3] years) than in individuals with T1DM (8.5 [4.9–11.8] years), with female preponderance in CFRD (59.1% vs. 47.5%; P < 0.01). CFRD patients had lower BMI standard deviation scores (−0.85 [−1.59 to −0.12] vs. +0.52 [−0.10 to +1.16]; P < 0.01) and lower HbA1c (6.87% vs. 7.97%; P < 0.01). Self-monitoring of blood glucose was more frequent in patients with T1DM (4.5 vs. 3.5; P < 0.01); 72% of CFRD patients received insulin. In insulin-treated patients, insulin dosage adjusted for age, sex, and diabetes duration differed significantly (T1DM: 0.79 IE per kilogram of body weight; CFRD: 0.83 IE per kilogram of body weight). Use of short-acting and long-acting insulin analogs was significantly more frequent in T1DM (47% vs. 39% and 37% vs. 28%; both P < 0.05). Metabolic control in CFRD patients without insulin was better compared with CFRD on insulin (HbA1c: 6.00 vs. 7.12; P < 0.01), but duration of disease was significantly shorter (0.8 years [0.1–2.4] compared with 2.4 years [0.6–4.6]). There was no significant difference for BMI standard deviations scores between CFRD patients with or without insulin treatment. CONCLUSIONS: Pediatric patients with CFRD show clear auxological and metabolic differences from those with T1DM, with different treatment choices.